Quetiapine, an Atypical Antipsychotic, Is Protective against Autoimmune-Mediated Demyelination by Inhibiting Effector T Cell Proliferation

Abstract

Quetiapine (Que), a commonly used atypical antipsychotic drug (APD), can prevent myelin from breakdown without immune attack. Multiple sclerosisis (MS), an autoimmune reactive inflammation demyelinating disease, is triggered by activated myelin-specific T lymphocytes (T cells). In this study, we investigated the potential efficacy of Que as an immune-modulating therapeutic agent for experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. Que treatment was initiated on the onset of MOG35–55 peptide induced EAE mice and the efficacy of Que on modulating the immune response was determined by Flow Cytometry through analyzing CD4+/CD8+ populations and the proliferation of effector T cells (CD4+CD25−) in peripheral immune organs. Our results show that Que dramatically attenuates the severity of EAE symptoms. Que treatment decreases the extent of CD4+/CD8+ T cell infiltration into the spinal cord and suppresses local glial activation, thereby diminishing the loss of mature oligodendrocytes and myelin breakdown in the spinal cord of EAE mice. Our results further demonstrate that Que treatment decreases the CD4+/CD8+ T cell populations in lymph nodes and spleens of EAE mice and inhibits either MOG35–55 or anti-CD3 induced proliferation as well as IL-2 production of effector T cells (CD4+CD25−) isolated from EAE mice spleen. Together, these findings suggest that Que displays an immune-modulating role during the course of EAE, and thus may be a promising candidate for treatment of MS.

Quetiapine mitigates the neuroinflammation and oligodendrocyte loss in the brain of C57BL/6 mouse following cuprizone exposure for one week

“…(2) QTP inhibited the release of TNF-α from interferon-γ-activated microglia in vitro (Bian et al, 2008); and (3) QTP displayed an immune-modulating role in the experimental autoimmune encephalomyelitis (Mei et al, 2012). In addition, we examined the effect of QTP on the toxic effect of CPZ on the oligodendrocytes (OLs), the myelin-producing cells which are most vulnerable to the toxic effects of CPZ among all the brain cells (Goldberg et al, 2013).…”

Amelioration of experimental autoimmune encephalomyelitis by clozapine is not associated with defective CD4 T cell responses

“…It has recently been shown that atypical antipsychotics such as risperidone, clozapine, and quetiapine are able to modulate the immune response and reduce disease effectively during EAE [10, 11]; however, the mechanism by which they mediate this effect is not yet fully understood. To better understand this mechanism, we used a dose of 60 mg/kg/day clozapine starting the day before immunization to effectively reduce the disease course of EAE (Fig.…”

Cognitive effects of acute restraint stress in male albino rats and the impact of pretreatment with quetiapine versus ghrelin

“…Also, the inhibitory e®ect of quetiapine on microglial activation has been described in the cuprizone induced demyelination mouse model (Zhang et al, 2008). Moreover, quetiapine has the potential capacity to reduce microglial and astroglial activation, and decrease myelin-speci¯c T cells in¯ltration (Mei et al, 2012).…”